Novel Buccal Xanthan Gum–Hyaluronic Acid Eutectogels with Dual Anti-Inflammatory and Antimicrobial Properties

Anuța, Valentina; Nica, Mihaela-Alexandra; Prisada, Răzvan-Mihai; Popa, Lăcrămioara; Velescu, Bruno Ștefan; Marinas, Ioana Cristina; Gaboreanu, Diana-Madalina; Ghica, Mihaela Violeta; Cocoș, Florentina Iuliana; Nicolae, Cristian Andi; Dinu-Pîrvu, Cristina-Elena

doi:10.3390/gels11030208

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Novel Buccal Xanthan Gum–Hyaluronic Acid Eutectogels with Dual Anti-Inflammatory and Antimicrobial Properties

by

Valentina Anuța

^1,2

,

Mihaela-Alexandra Nica

^1,2,

Răzvan-Mihai Prisada

^1,2,*

,

Lăcrămioara Popa

^1,2

,

Bruno Ștefan Velescu

^2,3,

Ioana Cristina Marinas

⁴

,

Diana-Madalina Gaboreanu

^4,5

,

Mihaela Violeta Ghica

^1,2

,

Florentina Iuliana Cocoș

^1,2,

Cristian Andi Nicolae

⁶ and

Cristina-Elena Dinu-Pîrvu

^1,2

¹

Department of Physical and Colloidal Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania

²

Innovative Therapeutic Structures Research and Development Centre (InnoTher), “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania

³

Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania

⁴

Research Institute of the University of Bucharest—ICUB, University of Bucharest, 91–95 Spl. Independentei, 050095 Bucharest, Romania

⁵

Departament of Botany and Microbiology, University of Bucharest, Faculty of Biology, Splaiul Independentei 91-95, 050095 Bucharest, Romania

⁶

National Institute for Research and Development in Chemistry and Petrochemistry—ICECHIM Bucharest, 202 Spl. Independentei, 060021 Bucharest, Romania

^*

Author to whom correspondence should be addressed.

Gels 2025, 11(3), 208; https://doi.org/10.3390/gels11030208 (registering DOI)

Submission received: 22 August 2024 / Revised: 3 March 2025 / Accepted: 10 March 2025 / Published: 15 March 2025

(This article belongs to the Special Issue Advanced Hydrogels for Regenerative Medicine and Tissue Engineering (3rd Edition))

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Abstract

Buccal drug delivery systems often struggle with poor drug solubility, limited adhesion, and rapid clearance, leading to suboptimal therapeutic outcomes. To address these limitations, we developed a novel hybrid eutectogel composed of xanthan gum (XTG), hyaluronic acid (HA), and a Natural Deep Eutectic Solvent (NADES) system (choline chloride, sorbitol, and glycerol in 2:1:1 mole ratio), incorporating 2.5% ibuprofen (IBU) as a model drug. The formulation was optimized using a face-centered central composite design to enhance the rheological, textural, and drug release properties. The optimized eutectogels exhibited shear-thinning behavior (flow behavior index, n = 0.26 ± 0.01), high mucoadhesion (adhesiveness: 2.297 ± 0.142 N·s), and sustained drug release over 24 h, governed by Higuchi kinetics (release rate: 237.34 ± 13.61 μg/cm²/min^1/2). The ex vivo residence time increased substantially with NADES incorporation, reaching up to 176.7 ± 23.1 min. An in vivo anti-inflammatory evaluation showed that the eutectogel reduced λ-carrageenan-induced paw edema within 1 h and that its efficacy was sustained in the kaolin model up to 24 h (p < 0.05), achieving comparable efficacy to a commercial 5% IBU gel, despite a lower drug concentration. Additionally, the eutectogel presented a minimum inhibitory concentration for Gram-positive bacteria of 25 mg/mL, and through direct contact, it reduced microbial viability by up to 100%. Its efficacy against Bacillus cereus, Enterococcus faecium, and Klebsiella pneumoniae, combined with its significant anti-inflammatory properties, positions the NADES-based eutectogel as a promising multifunctional platform for buccal drug delivery, particularly for inflammatory conditions complicated by bacterial infections.

Keywords: eutectogels; Natural Deep Eutectic Solvent (NADES); buccal drug delivery; mucosal drug delivery; xanthan gum; hyaluronic acid; anti-inflammatory activity; antimicrobial activity

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MDPI and ACS Style

Anuța, V.; Nica, M.-A.; Prisada, R.-M.; Popa, L.; Velescu, B.Ș.; Marinas, I.C.; Gaboreanu, D.-M.; Ghica, M.V.; Cocoș, F.I.; Nicolae, C.A.; et al. Novel Buccal Xanthan Gum–Hyaluronic Acid Eutectogels with Dual Anti-Inflammatory and Antimicrobial Properties. Gels 2025, 11, 208. https://doi.org/10.3390/gels11030208

AMA Style

Anuța V, Nica M-A, Prisada R-M, Popa L, Velescu BȘ, Marinas IC, Gaboreanu D-M, Ghica MV, Cocoș FI, Nicolae CA, et al. Novel Buccal Xanthan Gum–Hyaluronic Acid Eutectogels with Dual Anti-Inflammatory and Antimicrobial Properties. Gels. 2025; 11(3):208. https://doi.org/10.3390/gels11030208

Chicago/Turabian Style

Anuța, Valentina, Mihaela-Alexandra Nica, Răzvan-Mihai Prisada, Lăcrămioara Popa, Bruno Ștefan Velescu, Ioana Cristina Marinas, Diana-Madalina Gaboreanu, Mihaela Violeta Ghica, Florentina Iuliana Cocoș, Cristian Andi Nicolae, and et al. 2025. "Novel Buccal Xanthan Gum–Hyaluronic Acid Eutectogels with Dual Anti-Inflammatory and Antimicrobial Properties" Gels 11, no. 3: 208. https://doi.org/10.3390/gels11030208

APA Style

Anuța, V., Nica, M.-A., Prisada, R.-M., Popa, L., Velescu, B. Ș., Marinas, I. C., Gaboreanu, D.-M., Ghica, M. V., Cocoș, F. I., Nicolae, C. A., & Dinu-Pîrvu, C.-E. (2025). Novel Buccal Xanthan Gum–Hyaluronic Acid Eutectogels with Dual Anti-Inflammatory and Antimicrobial Properties. Gels, 11(3), 208. https://doi.org/10.3390/gels11030208

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Novel Buccal Xanthan Gum–Hyaluronic Acid Eutectogels with Dual Anti-Inflammatory and Antimicrobial Properties

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